Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00533321" target="_blank" >RIV/61388971:_____/20:00533321 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/20:00533321

Výsledek na webu

<a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008512" target="_blank" >https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008512</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.ppat.1008512" target="_blank" >10.1371/journal.ppat.1008512</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue

Popis výsledku v původním jazyce

Bordetella bronchisepticaandBordetella pertussisare closely related respiratory pathogens that evolved from a common bacterial ancestor. WhileB.bronchisepticahas an environmental reservoir and mostly establishes chronic infections in a broad range of mammals,B.pertussisis a human-specific pathogen causing acute pulmonary pertussis in infants and whooping cough illness in older humans. Both species employ a type III secretion system (T3SS) to inject a cytotoxic BteA effector protein into host cells. However, compared to the high BteA-mediated cytotoxicity ofB.bronchiseptica, the cytotoxicity induced byB.pertussisBteA (BpBteA) appears to be quite low and this has been attributed to the reduced T3SS gene expression inB.pertussis. We show that the presence of an alanine residue inserted at position 503 (A503) ofBpBteA accounts for its strongly attenuated cytotoxic potency. The deletion of A503 fromBpBteA greatly enhanced the cytotoxic activity ofB.pertussisB1917 on mammalian HeLa cells and expression ofBpBteA Delta A503 was highly toxic toSaccharomyces cerevisiaecells.Vice versa, insertion of A503 intoB.bronchisepticaBteA (BbBteA) strongly decreased its cytotoxicity to yeast and HeLa cells. Moreover, the production ofBpBteA Delta A503 increased virulence ofB.pertussisB1917 in the mouse model of intranasal infection (reduced LD50) but yielded less inflammatory pathology in infected mouse lungs at sublethal infectious doses. This suggests that A503 insertion in the T3SS effectorBpBteA may represent an evolutionary adaptation that fine-tunesB.pertussisvirulence and host immune response.

Název v anglickém jazyce

Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue

Popis výsledku anglicky

Bordetella bronchisepticaandBordetella pertussisare closely related respiratory pathogens that evolved from a common bacterial ancestor. WhileB.bronchisepticahas an environmental reservoir and mostly establishes chronic infections in a broad range of mammals,B.pertussisis a human-specific pathogen causing acute pulmonary pertussis in infants and whooping cough illness in older humans. Both species employ a type III secretion system (T3SS) to inject a cytotoxic BteA effector protein into host cells. However, compared to the high BteA-mediated cytotoxicity ofB.bronchiseptica, the cytotoxicity induced byB.pertussisBteA (BpBteA) appears to be quite low and this has been attributed to the reduced T3SS gene expression inB.pertussis. We show that the presence of an alanine residue inserted at position 503 (A503) ofBpBteA accounts for its strongly attenuated cytotoxic potency. The deletion of A503 fromBpBteA greatly enhanced the cytotoxic activity ofB.pertussisB1917 on mammalian HeLa cells and expression ofBpBteA Delta A503 was highly toxic toSaccharomyces cerevisiaecells.Vice versa, insertion of A503 intoB.bronchisepticaBteA (BbBteA) strongly decreased its cytotoxicity to yeast and HeLa cells. Moreover, the production ofBpBteA Delta A503 increased virulence ofB.pertussisB1917 in the mouse model of intranasal infection (reduced LD50) but yielded less inflammatory pathology in infected mouse lungs at sublethal infectious doses. This suggests that A503 insertion in the T3SS effectorBpBteA may represent an evolutionary adaptation that fine-tunesB.pertussisvirulence and host immune response.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PLoS Pathogens

ISSN

1553-7366

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

20

Strana od-do

e1008512

Kód UT WoS článku

000561392400003

EID výsledku v databázi Scopus

2-s2.0-85089787575